Clinical outcomes of etoposide and cytarabine as consolidation in elderly patients with primary CNS lymphoma.

BACKGROUND: A consolidation strategy has not been established for transplant-ineligible elderly patients with primary central nervous system lymphoma (PCNSL). In this study, we aimed to retrospectively evaluate the clinical outcomes of etoposide and cytarabine (EA) as consolidation chemotherapy for transplant-ineligible patients with PCNSL following high-dose methotrexate (MTX)-based induction chemotherapy. MATERIALS AND METHODS: Between 2015 and 2021, newly diagnosed transplant-ineligible patients with PCNSL with diffuse large B-cell lymphoma were consecutively enrolled. All enrolled patients were over 60 years old and received EA consolidation after achieving a complete or partial response following induction chemotherapy. RESULTS: Of the 85 patients who achieved a complete or partial response to MTX-based induction chemotherapy, 51 received EA consolidation chemotherapy. Among the 25 (49.0%, 25/51) patients in partial remission before EA consolidation, 56% (n = 14) achieved complete remission after EA consolidation. The median overall survival and progression-free survival were 43 and 13 months, respectively. Hematological toxicities were most common, and all patients experienced grade 4 neutropenia and thrombocytopenia. Forty-eight patients experienced febrile neutropenia during consolidation chemotherapy, and 4 patients died owing to treatment-related complications. CONCLUSION: EA consolidation chemotherapy for transplant-ineligible, elderly patients with PCNSL improved response rates but showed a high relapse rate and short progression-free survival. The incidences of treatment-related mortality caused by hematologic toxicities and severe infections were very high, even after dose modification. Therefore, the use of EA consolidation should be reconsidered in elderly patients with PCNSL.

A Multicenter Analysis of Clinical Features and Long-Term Outcomes of POEMS Syndrome in Korea.

BACKGROUND: POEMS syndrome is a rare form of plasma cell dyscrasia characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal proteins, and skin changes. Owing to its low incidence, there are few reports regarding this syndrome. This multicenter study included 84 patients diagnosed with POEMS syndrome in South Korea. METHODS: We retrospectively evaluated 84 patients diagnosed with POEMS syndrome at 8 hospitals in South Korea between January 2000 and October 2022. The clinical characteristics and treatment outcomes were analyzed. RESULTS: The median patient age was 53 years (range, 26-77 years), and 63.1% of the patients were male. All patients had peripheral neuropathy, and 81 (96.4%) had monoclonal plasma cell proliferation. Plasma vascular endothelial growth factor levels were available for 32 patients with a median of 821 pg/mL (range, 26-12,900 pg/mL). Other common features included skin changes (54.2%), volume overload (71.4%), and organomegaly (72.6%). Of the 84 patients, 75 received initial treatment (local radiotherapy, 6 [8.0%]; chemotherapy, 17 [22.7%]; both chemotherapy and local radiotherapy, 9 [12.0%]), upfront autologous stem cell transplantation (ASCT), 43 (57.3%; with induction chemotherapy, n = 12, 16.0%; without induction chemotherapy, n = 31, 41.3%). The median follow-up duration was 40.7 months. The 5-year overall survival (OS) was 78%, and the 5-year progression-free survival (PFS) was 55%. Patients who underwent upfront ASCT and were diagnosed after 2014 had a longer OS and PFS. CONCLUSION: The demographics of Korean patients with POEMS syndrome were similar to those reported previously. Because of the introduction of new treatment agents and the reduced rate of transplant-related mortality related to ASCT, the treatment outcomes of Korean patients with POEMS syndrome have improved in recent years.

A population pharmacokinetic model of methotrexate in Korean patients with haematologic malignancy.

AIMS: This study was conducted to develop a population pharmacokinetic (PK) model of methotrexate in Korean patients with haematologic malignancy, identify factors affecting methotrexate PK, and propose an optimal dosage regimen for the Korean population. METHODS: Data were retrospectively collected from 188 patients with acute leukaemia or non-Hodgkin's lymphoma who were admitted to Severance Hospital during the period from November 2005 to January 2016. Using demographic factors and laboratory results as potential covariates for PK parameters, model development was performed using NONMEM and optimal dosing regimens were developed using the final PK model. RESULTS: A two-compartment model incorporating body weight via allometry best described the data, yielding typical parameter values of 25.09 L for central volume of distribution ( V 1 ), 17.65 L for peripheral volume of distribution ( V 2 ), 12.89 L/h for clearance (CL) and 0.655 L/h for inter-compartmental clearance in a 50 kg patient. Covariate analyses showed that, at the weight of 50 kg, CL decreased by 0.11 L/h for each 1-year increase in age above 14 years old and decreased 0.8-fold when serum creatinine level doubled, indicating the importance of age-specific dose individualization in methotrexate treatment. Volume of distribution at steady state derived from PK parameters (= V 1 + V 2 ) was 0.85 L/kg, which was similar to those in the Western or Chinese populations. Optimal doses simulated from the final model successfully produced the PK measures close to the target chosen. CONCLUSIONS: The population PK model and optimal dosage regimens developed in this study can be used as a basis to achieve precision dosing in Korean patients with haematologic malignancy.

Utility of Plasma Microbial Cell-Free DNA Whole-Genome Sequencing for Diagnosis of Invasive Aspergillosis in Patients With Hematologic Malignancy or COVID-19.

BACKGROUND: We evaluated the clinical accuracy and utility of whole-genome sequencing (WGS) of plasma microbial cell-free DNA (cfDNA) as a novel noninvasive method in diagnosing invasive aspergillosis (IA) in patients with hematologic malignancy (HM) or coronavirus disease 2019 (COVID-19). METHODS: Adults with HM or COVID-19 and suspected IA were recruited. IA cases were retrospectively diagnosed according to EORTC/MSG definitions and ECMM/ISHAM criteria for HM and COVID-19 patients, respectively. The results of cfDNA WGS were compared with the conventional diagnosis. RESULTS: Microbial cfDNA WGS was performed 53 times from 41 participants (19 from HM, 16 from COVID-19, and 7 from the control group). In participants with HM, Aspergillus cfDNA was detected in 100% of proven IA and 91.7% of probable IA cases. In participants with COVID-19, 50.0% of probable IA were positive for Aspergillus in cfDNA WGS. Concordance between Aspergillus cfDNA detection and proven/probable IA conventional diagnosis was significantly higher in participants with HM than in those with COVID-19. IA diagnosed using EORTC/MGS definitions showed significantly high concordance between Aspergillus cfDNA detection and proven/probable IA. CONCLUSIONS: Aspergillus cfDNA detection strongly correlated with proven/probable IA diagnosed using EORTC/MSG definitions and could be used as an additional diagnostic tool for IA.

Is an Anatomical Suprapectineal Quadrilateral Surface Plate Superior to Previous Fixation Methods for Anterior Column-Posterior Hemitransverse Acetabular Fractures Typical in the Elderly?: A Biomechanical Study.

Background: This study aimed to compare the mechanical characteristics of four fixation methods including an anatomical suprapectineal quadrilateral surface (QLS) plate in hemipelvic models of anterior column-posterior hemitransverse acetabular fractures typical in elderly patients. Methods: In total, 24 composite hemipelvic models were used and allocated to four groups: group 1, pre-contoured anatomical suprapectineal QLS plate; group 2, suprapectineal reconstruction plate with two periarticular long screws; group 3, suprapectineal reconstruction plate with a buttress reconstruction plate; group 4, suprapectineal reconstruction plate with a buttress T-plate. Axial structural stiffness and displacement of each column fragment in four different fixation constructs were compared. Results: Multiple group comparisons of axial structural stiffness demonstrated significant difference (p = 0.001). Although there was no significant difference between groups 1 and 2 (p = 0.699), group 1 showed greater stiffness than groups 3 and 4 (p = 0.002 and 0.002, respectively). Group 1 showed less displacement in the anterior region of the anterior fragment than group 4 (p = 0.009) and in the posterior region than groups 3 and 4 (p = 0.015 and p = 0.015, respectively). However, group 1 demonstrated greater displacement than group 2 in the posterior region of the posterior fragment (p = 0.004), while showing similar displacement to groups 3 and 4. Conclusions: The anatomical suprapectineal QLS plate provided the mechanical stability comparable or superior to other existing fixations in osteoporotic models of anterior column-posterior hemitransverse acetabular fractures typical in the elderly. However, additional plate modification would be needed for better stability and outcomes.

Biomechanical Evaluation of Lateral Lumbar Interbody Fusion with Various Fixation Options for Adjacent Segment Degeneration: A Finite Element Analysis.

OBJECTIVE: Adjacent segment degeneration (ASD) is a common phenomenon after lumbar fusion. Lateral lumbar interbody fusion (LLIF) may provide an alternative treatment method for ASD. This study used finite element analysis to evaluate the biomechanical effects of LLIF with various fixation options and identify an optimal surgical strategy for ASD. METHODS: A validated L1-S1 finite element model was modified for simulation. Six finite element models of the lumbar spine were created and were divided into group 1 (L4-5 posterior lumbar interbody fusion [PLIF] + L3-4 LLIF) and group 2 (L5-S1 PLIF + L4-5 LLIF). Each group consisted of 1) cage-alone, 2) cage + lateral screw fixation (LSF), and 3) cage + bilateral pedicle screw fixation (BPSF) models. The range of motion, intradiscal pressure, and facet loads of adjacent segments as well as interbody cage stress were analyzed. RESULTS: The stress on the LLIF cage-superior endplate interface was highest in the cage-alone model followed by the cage + LSF model and cage + BPSF model. The increase in range of motion, intradiscal pressure, and facet loads at the adjacent segment was highest in the cage + BPSF model followed by the cage + LSF model and cage-alone model. However, the biomechanical effect on the adjacent segment seemed similar in the cage-alone and cage + LSF models. CONCLUSIONS: LLIF with BPSF is recommended when performing LLIF surgery for ASD after L4-5 and L5-S1 PLIF. Considering cage subsidence and biomechanical effects on the adjacent segment, LLIF with LSF may be a suboptimal option for ASD surgery.

DRP1 Inhibition Enhances Venetoclax-Induced Mitochondrial Apoptosis in TP53-Mutated Acute Myeloid Leukemia Cells through BAX/BAK Activation.

Although TP53 mutations in acute myeloid leukemia (AML) are associated with poor response to venetoclax, the underlying resistance mechanism remains unclear. Herein, we investigated the functional role of dynamin-related protein 1 (DRP1) in venetoclax sensitivity in AML cells with respect to TP53 mutation status. Effects of DRP1 inhibition on venetoclax-induced cell death were compared in TP53-mutated (THP-1 and Kasumi-1) and TP53 wild-type leukemia cell lines (MOLM-13 and MV4-11), as well as in primary AML cells obtained from patients. Venetoclax induced apoptosis in TP53 wild-type AML cells but had limited effects in TP53-mutated AML cells. DRP1 expression was downregulated in MOLM-13 cells after venetoclax treatment but was unaffected in THP-1 cells. Cotreatment of THP-1 cells with venetoclax and a TP53 activator NSC59984 downregulated DRP1 expression and increased apoptosis. Combination treatment with the DRP1 inhibitor Mdivi-1 and venetoclax significantly increased mitochondria-mediated apoptosis in TP53-mutated AML cells. The combination of Mdivi-1 and venetoclax resulted in noticeable downregulation of MCL-1 and BCL-xL, accompanied by the upregulation of NOXA, PUMA, BAK, and BAX. These findings suggest that DRP1 is functionally associated with venetoclax sensitivity in TP53-mutated AML cells. Targeting DRP1 may represent an effective therapeutic strategy for overcoming venetoclax resistance in TP53-mutated AML.

Development of a Next-generation Sequencing-based Gene Panel Test to Detect Measurable Residual Disease in Acute Myeloid Leukemia.

Background: AML is a heterogeneous disease, and despite intensive therapy, recurrence is still high in AML patients who achieve the criterion for cytomorphologic remission (residual tumor burden [measurable residual disease, MRD]<5%). This study aimed to develop a targeted next-generation sequencing (NGS) panel to detect MRD in AML patients and validate its performance. Methods: We designed an error-corrected, targeted MRD-NGS panel without using physical molecular barcodes, including 24 genes. Fifty-four bone marrow and peripheral blood samples from 23 AML patients were sequenced using the panel. The panel design was validated using reference material, and accuracy was assessed using droplet digital PCR. Results: Dilution tests showed excellent linearity and a strong correlation between expected and observed clonal frequencies (R>0.99). The test reproducibly detected MRD in three dilution series samples, with a sensitivity of 0.25% for single-nucleotide variants. More than half of samples from patients with morphologic remission after one month of chemotherapy had detectable mutations. NGS-MRD positivity for samples collected after one month of chemotherapy tended to be associated with poor overall survival and progression-free survival. Conclusions: Our highly sensitive and accurate NGS-MRD panel can be readily used to monitor most AML patients in clinical practice, including patients without gene rearrangement. In addition, this NGS-MRD panel may allow the detection of newly emerging clones during clinical relapse, leading to more reliable prognoses of AML.

Complete mitochondrial genome of Macromia manchurica Asahina, 1964 (Odonata: Macromiidae).

We describe the first time sequencing and assembly of the complete mitochondrial genome of Macromia manchurica Asahina, 1964 (Odonata; Macromiidae; Macromia). The mitochondrial genome of M. manchurica was found to be 15,560 bp. It contains thirteen protein-coding genes (PCGs), 22 transfer RNAs (tRNAs), two ribosomal RNAs (rRNAs), and AT-rich region. The overall base composition of A. japonicus is A-38.6%, C-17.0%, G-12.5%, and T-31.9%. A phylogenetic analysis of 14 species within the order Odonata and order Ephemeroptera suggested that Macromia amphigena is most closely related to M. manchurica.

Complete mitochondrial genome of Appasus japonicus Vuillefroy, 1864 (Hemiptera: Belostomatidae).

We describe the initial sequencing and assembly of the complete mitochondrial genome of Appasus japonicus Vuillefroy, 1864 (Hemiptera; Belostomatidae; Appasus). The mitochondrial genome of A. japonicus was found to be 18,608 bp. It contains thirteen protein-coding genes (PCGs), 22 transfer RNAs (tRNAs), two ribosomal RNAs (rRNAs) and an AT-rich region. The overall base composition of A. japonicus is A-41.9%, C-17.5%, G-11.9%, and T-28.7%. A phylogenetic analysis of 21 species within the order Hemiptera suggests that Diplonychus rusticus is most closely related to A. japonicus.

Biomechanical Comparison of Multilevel Lumbar Instrumented Fusions in Adult Spinal Deformity According to the Upper and Lower Fusion Levels: A Finite Element Analysis.

Multilevel lumbar fusion with posterior pedicle screw fixation is a widely performed surgical procedure for the management of adult spinal deformity. However, there has not been a comprehensive biomechanical study on the different types of fusion levels in terms of stability and possible complications. We aimed to investigate the biomechanical properties of multilevel lumbar fusion according to different types of upper and lower fusion levels. Six different types of fusions were performed using three-dimensional finite element models. Type A and B referred to the group of which upper fusion level was L1 and T10, respectively. Subtype 1, 2, and 3 referred to the group of which lower fusion level was L5, S1, and ilium, respectively (A1, L1-L5; A2, L1-S1; A3, L1-ilium; B1, T10-L5; B2, T10-S1; B3, T10-ilium). Flexion, extension, axial rotation, and lateral bending moments were applied, and the risk of screw loosening and failure and adjacent segment degeneration (ASD) was analyzed. Stress at the bone-screw interface of type B3 was lowest in overall motions. The risk of screw failure showed increasing pattern as the upper and lower levels extended in all motions. Proximal range of motion (ROM) increased as the lower fusion level changed from L5 to S1 and the ilium. For axial rotation, type B3 showed higher proximal ROM (16.2°) than type A3 (11.8°). In multilevel lumbar fusion surgery for adult spinal deformity, adding iliac screws and increasing the fusion level to T10-ilium may lower the risk of screw loosening. In terms of screw failure and proximal ASD, however, T10-ilium fusion has a higher potential risk compared with other fusion types. These results will contribute for surgeons to provide adequate patient education regarding screw failure and proximal ASD, when performing multilevel lumbar fusion.

Low genetic diversity, local-scale structure, and distinct genetic integrity of Korean chum salmon (Oncorhynchus keta) at the species range margin suggest a priority for conservation efforts.

Chum salmon (Oncorhynchus keta) is an ecologically and economically important species widely distributed across the North Pacific Ocean. However, the population size of this fishery resource has declined globally. Identifying genetic integrity, diversity and structure, and phylogenetic relationships of wild populations of O. keta over an entire species' range is central for developing its effective conservation and management plans. Nevertheless, chum salmon from the Korean Peninsula, which are comprised of its southwestern range margins, have been overlooked. By using mtDNA control region and 10 microsatellite loci, we here assessed the genetic diversity and structure for 16 populations, including 10 wild and six hatchery populations, encompassing the species entire geographic range in South Korea. The analyses showed that genetic diversity is significantly higher for wild than for hatchery populations. Both marker sets revealed significant genetic differentiation between some local populations. Comparisons of six wild and their respective hatchery populations indicated that allele/haplotype frequencies considerably differ, perhaps due to a strong founder effect and/or homogenizing of hatchery populations for stocking practice. Despite its single admixed gene pool for the Korean chum salmon, some local populations housing their own unique lineages should be accorded with a high priority to safeguard their genetic integrities. The results of our comparative analyses of the Korean population with other North Pacific chum salmons (inhabiting regions of Japan, Russia, and North America) revealed a lower diversity but higher contribution to the overall species-level genetic diversity, and also its unique genetic integrity. These findings advocate for the evolutionary significance of the Korean population for species-level conservation.

Therapy-related Acute Lymphoblastic Leukaemia has a Unique Genetic Profile Compared to De Novo Acute Lymphoblastic Leukaemia.

Background: Unlike therapy-related myeloid neoplasms, therapy-related acute lymphoblastic leukaemia (tr-ALL) is poorly defined due to its rarity. However, increasing reports have demonstrated that tr-ALL is a distinct entity with adverse genetic features and clinical outcomes. Methods: We compared the clinicopathological characteristics and outcomes of patients diagnosed with tr-ALL (n = 9) or de novo ALL (dn-ALL; n = 162) at a single institution from January 2012 to March 2021. The mutational landscapes of eight tr-ALL and 63 dn-ALL patients were compared from a comprehensive next-generation sequencing panel. Results: All tr-ALL patients had the B-cell phenotype. The most frequently mutated genes were IKZF1 (37%), CDKN2A (14%), SETD2 (13%), and CDKN2B (11%) in dn-ALL, whereas TP53 (38%) and RB1 (25%) mutations were most common in tr-ALL. tr-ALL patients did not show a statistically significant difference in overall survival (p = 0.70) or progression-free survival (p = 0.94) compared to dn-ALL patients. Conclusions: In this study, we determined the clinical and genetic profiles of Korean patients with tr-ALL. We found alterations in genes constituting the TP53/RB1 pathway are more frequent in tr-ALL. Due to the rarity of the disease, multi-institutional studies involving a larger number of patients are required in future study.

Using Single-Crystal Graphene to Form Arrays of Nanocapsules Enabling the Observation of Light Elements in Liquid Cell Transmission Electron Microscopy.

We have designed and fabricated a TEM (transmission electron microscopy) liquid cell with hundreds of graphene nanocapsules arranged in a stack of two Si3N4-x membranes. These graphene nanocapsules are formed on arrays of nanoholes patterned on the Si3N4-x membrane by focused ion beam milling, allowing for better resolution than for the conventional graphene liquid cells, which enables the observation of light elements, such as atomic structures of silicon. We suggest that multiple nanocapsules provide opportunities for consecutive imaging under the same conditions in a single liquid cell. The use of single-crystal graphene windows offers an excellent signal-to-noise ratio and high spatial resolution. The motion of silicon nanoparticles (a low atomic number (Z) material) interacting with nanobubbles was observed, and analyzed, in detail. Our approach will help advance liquid-phase TEM observations by providing a straightforward method to encapsulate liquid between monolayers of various 2-dimensional materials.

Real-world data on prognostic value of measurable residual disease assessment by fragment analysis or next-generation sequencing in multiple myeloma.

Measurable residual disease (MRD) negativity is a strong prognostic indicator in multiple myeloma (MM). However, the optimal use of MRD in daily clinical practice has been hampered by the limited feasibility of MRD testing. Therefore, we examined the clinical relevance of commercially available MRD modalities based on clonality assays by fragment analysis with IdentiClone® (n = 73 patients) and next-generation sequencing (NGS) with LymphoTrack® (n = 116 patients) in newly diagnosed patients with MM who received autologous stem cell transplantation (ASCT). MRD was assessed at the end of induction (pre-ASCT) and/or at 100 days after ASCT (post-ASCT). MRD could not predict survival when assessed by fragment analysis. However, NGS-based MRD negativity at pre- or post-ASCT was beneficial in terms of progression-free and overall survival. Moreover, NGS-based MRD negativity was independently associated with improved progression-free and overall survival, and MRD-positive patients both pre- and post-ASCT had worst outcome. Indeed, initial adverse prognostic features by high-risk cytogenetics could be mitigated upon achieving MRD negativity by NGS. We demonstrate the feasibility and clinical benefit of achieving MRD negativity by commercially available clonality-based MRD assays in MM and support incorporating NGS, but not fragment analysis, to tailor therapeutic strategies in real-world practice.

Cytogenetic testing by fluorescence in situ hybridization is improved by plasma cell sorting in multiple myeloma.

Accurate detection of cytogenetic abnormalities has become more important for improving risk-adapted treatment strategies in multiple myeloma (MM). However, precise cytogenetic testing by fluorescence in situ hybridization (FISH) is challenged by the dilution effect of bone marrow specimens and poor growth of plasma cells ex vivo. It has been suggested that FISH should be performed in combination with plasma cell enrichment strategies. We examined cytogenetic abnormalities in newly diagnosed MM and compared the efficacy of three different enrichment modalities for FISH: direct FISH (n = 137), fluorescence immunophenotyping and interphase cytogenetics as a tool for the investigation of neoplasms (FICTION) technique (n = 224), and a plasma cell sorting FISH with fluorescence-activated cell sorter (FACS) (n = 132). FISH disclosed cytogenetic abnormalities in 38.0% of samples by direct FISH, 56.3% by FICTION, and 95.5% by FACS-FISH, and the percentage of cells with abnormal signals detected by FISH was significantly higher by FACS-FISH than direct FISH or FICTION. Our results suggest that the efficacy of FISH is dependent on the plasma cell enrichment modalities and reveal that plasma cell sorting FISH with FACS enables better detection of cytogenetic abnormalities in diagnostic MM samples.

Comparative analysis of mesenchymal stem cells cultivated in serum free media.

Stem cells are attractive candidates for the regeneration of tissue and organ. Mesenchymal stem cells (MSCs) have been extensively investigated for their potential applications in regenerative medicine and cell therapy. For developing effective stem cell therapy, the mass production of consistent quality cells is required. The cell culture medium is the most critical aspect of the mass production of qualified stem cells. Classically, fetal bovine serum (FBS) has been used as a culture supplement for MSCs. Due to the undefined and heterologous composition of animal origin components in FBS, efforts to replace animal-derived components with non-animal-derived substances led to safe serum free media (SFM). Adipose derived mesenchymal stem cells (ADSCs) cultivated in SFM provided a more stable population doubling time (PDT) to later passage and more cells in a shorter time compared to FBS containing media. ADSCs cultivated in SFM had lower cellular senescence, lower immunogenicity, and higher genetic stability than ADSCs cultivated in FBS containing media. Differential expression analysis of mRNAs and proteins showed that the expression of genes related with apoptosis, immune response, and inflammatory response were significantly up-regulated in ADSCs cultivated in FBS containing media. ADSCs cultivated in SFM showed similar therapeutic efficacy in an acute pancreatitis mouse model to ADSCs cultivated in FBS containing media. Consideration of clinical trials, not only pre-clinical trial, suggests that cultivation of MSCs using SFM might offer more safe cell therapeutics as well as repeated administration due to low immunogenicity.

Complete mitochondrial genome of large dragonfly (Macromia amphigena).

The complete mitochondrial genome of Macromia amphigena (Odonata; Macromiidae; Macromia) was sequenced and found to be 15,594 bp in length including 37 genes (thirteen protein-coding genes (PCGs), 22 transfer RNAs (tRNAs) and two ribosomal RNAs (rRNAs) and a non-coding region). The overall GC content of the mitochondrial genome for M. amphigena was 28.4%. A phylogenetic analysis conducted for 13 species within the order Odonata suggested that Macromia daimoji is the most closely related to M. amphigena.

Predictive Factors of Event-Free Survival at 24 Months in Patients with Peripheral T-Cell Lymphoma: A Retrospective Study.

PURPOSE: Event-free survival at 24 months (EFS24) is known to be a surrogate marker for overall survival (OS) for patients with peripheral T-cell lymphoma (PTCL). We examined the role of EFS24 in PTCL compared to diffuse large B-cell lymphoma (DLBCL), and then assessed the clinical predictive factors of achieving EFS24. MATERIALS AND METHODS: Patients with newly diagnosed PTCL treated with anthracycline-based chemotherapy were included. Subsequent OS was defined as the time elapsed from 24 months after diagnosis until death from any cause in those who achieved EFS24. RESULTS: Overall, 153 patients were evaluated, and 51 patients (33.3%) achieved EFS24. Patients who achieved EFS24 showed superior OS compared to patients who did not (p < 0.001). EFS24 could stratify the subsequent OS although it did not reach to that of the general population. After matching the PTCL group to the DLBCL group based on the international prognostic index, the subsequent OS in patients who achieved EFS24 was similar between the two groups (p=0.094). Advanced stage was a significant factor to predict the failing EFS24 by multivariable analysis (p < 0.001). CONCLUSION: Patients with PTCL who achieve EFS24 could have a favorable subsequent OS. Since advanced disease stage is a predictor of EFS24 failure, future efforts should focus on developing novel therapeutic strategies for PTCL patients presenting with advanced disease.

Ig Gene Clonality Analysis Using Next-Generation Sequencing for Improved Minimal Residual Disease Detection with Significant Prognostic Value in Multiple Myeloma Patients.

Next-generation sequencing (NGS) of rearranged Ig genes is an effective technology for identifying pathologic clonal cells in multiple myeloma (MM) and tracking minimal residual disease. The clinical effect of implementing NGS in Ig gene clonality analysis was evaluated via a retrospective chart review. A total of 312 patients diagnosed with MM were enrolled in the study. Ig gene clonality was determined by fragment analysis using BIOMED-2 multiplex PCR assays and by NGS using the LymphoTrack IGH FR1 Assay and LymphoTrack IGK Assay. The clonality detection rates in diagnostic samples obtained using fragment analysis and NGS were 96.7% and 95.4%, respectively (statistically nonsignificant difference; P = 0.772). Among samples of patients in complete remission, the clonality detection rates obtained using fragment analysis and NGS were 33.3% and 60.3%, respectively (statistically significant difference; P = 0.034). Progression-free survival was significantly longer in negative than positive patients by NGS analysis (P = 0.03). Clonality detection by NGS-based methods using IGH FR1 and IGK assays in routine clinical practice is feasible, provides good clonality detection rates in diagnostic samples, and allows monitoring of samples in MM patients with significant prognostic value.